Format

Send to

Choose Destination
Cell Rep. 2016 Sep 27;17(1):149-164. doi: 10.1016/j.celrep.2016.08.090.

The Homeobox Transcription Factor RHOX10 Drives Mouse Spermatogonial Stem Cell Establishment.

Author information

1
School of Medicine, Department of Reproductive Medicine, University of California at San Diego, La Jolla, CA 92093, USA.
2
Department of Bioengineering, University of California at San Diego, La Jolla, CA 92093, USA.
3
Obstetrics, Gynecology, and Reproductive Sciences, University of Pittsburgh School of Medicine, Magee-Womens Research Institute, Pittsburgh, PA 15213, USA.
4
Reproductive Biology Group, Division of Developmental Biology, Faculty of Science, Department of Biology, Utrecht University, 3584 CH Utrecht, the Netherlands.
5
School of Medicine, Department of Reproductive Medicine, University of California at San Diego, La Jolla, CA 92093, USA; Institute of Genomic Medicine, University of California, San Diego, La Jolla, CA 92093, USA. Electronic address: mfwilkinson@ucsd.edu.

Abstract

The developmental origins of most adult stem cells are poorly understood. Here, we report the identification of a transcription factor-RHOX10-critical for the initial establishment of spermatogonial stem cells (SSCs). Conditional loss of the entire 33-gene X-linked homeobox gene cluster that includes Rhox10 causes progressive spermatogenic decline, a phenotype indistinguishable from that caused by loss of only Rhox10. We demonstrate that this phenotype results from dramatically reduced SSC generation. By using a battery of approaches, including single-cell-RNA sequencing (scRNA-seq) analysis, we show that Rhox10 drives SSC generation by promoting pro-spermatogonia differentiation. Rhox10 also regulates batteries of migration genes and promotes the migration of pro-spermatogonia into the SSC niche. The identification of an X-linked homeobox gene that drives the initial generation of SSCs has implications for the evolution of X-linked gene clusters and sheds light on regulatory mechanisms influencing adult stem cell generation in general.

KEYWORDS:

Rhox; germ cell; germ line stem cell; gonocytes; homeobox; prospermatogonia; spermatogenesis; spermatogonia; spermatogonial stem cells; transcription factor

PMID:
27681428
PMCID:
PMC5063083
DOI:
10.1016/j.celrep.2016.08.090
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center